THE BETA-OXIDATION OF ARACHIDONIC-ACID AND THE SYNTHESIS OF DOCOSAHEXAENOIC ACID ARE SELECTIVELY AND CONSISTENTLY ALTERED IN SKIN FIBROBLASTS FROM 3 ZELLWEGER PATIENTS VERSUS X-ADRENOLEUKODYSTROPHY, ALZHEIMER AND CONTROL SUBJECTS

The beta-oxidation of [H-3] arachidonic acid (AA; 20:4 n-6) and the co nversion of [1-C-14]eicosapentaenoic acid (EPA, 20:5 n-3) to docosahex aenoic acid (DHA, 22:6 n-3) have been studied in skin fibroblasts from patients with inherited peroxisomal diseases, such as Zellweger (ZW) and X-linked adrenoleukodystrophy (X-ALD), from patients with Alzheime r's disease (AD), a noninherited neuropathology, and from controls. EP A is not converted to DHA, while there is enhanced formation of the in termediate product 22:5 n-3 in ZW, when compared to X-ALD, AD and cont rols. We also confirmed that AA is not beta-oxidized to 4,7,10-hexadec atrienoic acid (16:3), a metabolite produced by peroxisomes, while bei ng more effectively converted to the elongation product 22:4, in ZW, i n comparison to X-ALD, AD and controls. The data demonstrate a defect in DHA synthesis and in AA beta-oxidation, and the occurrence of assoc iated adaptative modifications in the metabolism of these long chain P UFA, in th ree Italian ZW patients. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.